Mol Pain
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Pain and anxiety are two common and undertreated non-motor symptoms in Parkinson's disease (PD), which affect the life quality of PD patients, and the underlying mechanisms remain unclear. As an important subtype of adenylyl cyclases (ACs), adenylyl cyclase subtype 1 (AC1) is critical for the induction of cortical long-term potentiation (LTP) and injury induced synaptic potentiation in the cortical areas including anterior cingulate cortex (ACC) and insular cortex (IC). Genetic deletion of AC1 or pharmacological inhibition of AC1 improved chronic pain and anxiety in different animal models. ⋯ By using genetic knockout mice, we found that AC1 knockout mice showed reduced pain and anxiety symptoms after MPTP administration, but not AC8 knockout mice. In summary, genetic deletion of AC1 or pharmacological inhibition of AC1 improved pain and anxiety symptoms in PD model mice, but didn't affect motor function. These results suggest that NB001 is a potential drug for the treatment of pain and anxiety symptoms in PD patients by inhibiting AC1 target.
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Background: Migraine is a common type of primary headache with disabling brain dysfunction. It has been found that pituitary adenylate cyclase activating polypeptide (PACAP) is involved in the pathogenesis of migraine, however, the role of PACAP and its receptors in chronic migraine remains unclear. Therefore, the present study aimed to explore the changes of PACAP and its receptors in different duration after recurrent dural inflammation soup stimulations and to investigate the co-expression between PACAP and calcitonin gene-related peptide (CGRP). ⋯ While the co-expression between PACAP and CGRP reached the peak in IS-7 group after repetitive IS stimulation, and then decreased. Conclusions: This study demonstrated that repetitive chemical stimulations induced a gradual decrease of PACAP in the TNC, while the PACAP and PAC1 receptor expression in TG showed dynamical changes of increasing first and then decreasing after repeated IS administration. These results suggested exhaustion of PACAP could be involved in the duration of chronic migraine and implied PACAP may contribute to the pathology of migraine through the PAC1 receptor, which was associated with CGRP.
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Background: Remifentanil-induced postoperative hyperalgesia (RIH) refers to a state of hyperalgesia or aggravated pre-existing pain after remifentanil exposure. There has been considerable interest in understanding and preventing RIH. However, the mechanisms responsible for RIH are still not completely understood. ⋯ In addition, TRPA1 antagonist HC-030031 also alleviated mechanical pain and decreased TRPA1 expression in RIH without affecting TLR4 signaling in DRG. Conclusions: Taken together, these results suggested that activation of TLR4 signaling pathway engaged in the development of RIH by regulating TRPA1 in DRG neurons. Blocking TLR4 and TRPA1 might serve as a promising therapeutic strategy for RIH.